Project Summary/Abstract Central nervous system control over hedonic processing plays a critical role in directing animals towards situations that elicit pleasure and avoiding those that lead to discomfort/aversion. Aberrant affective processing is linked to many psychiatric illnesses including substance use disorders which are associated with anhedonia (the loss of pleasure to reward) and the emergence of dysphoric emotional states. Taste reactivity can be utilized as a preclinical model to gain insight into the neural mechanisms underlying hedonic processing. In conditioned taste aversion (CTA) a palatable sucrose solution that normally elicits appetitive taste reactivity is devalued through an association with malaise-inducing lithium chloride. When rats are subsequently and repeatedly exposed to the devalued sucrose, they exhibit extinction learning where aversive taste reactivity is suppressed and the positive hedonic valence of sucrose is restored. The ventral medial prefrontal cortex (subgenual cingulate in humans, infralimbic cortex [IL] in rats) has been implicated in the suppression of aversive emotional states in both humans and animals, and in the rat, the IL sends a robust glutamatergic projection that spans the rostral-caudal extent of the nucleus accumbens shell (NAcSh). Further, the rostral and caudal regions of the NAcSh have opposing and unique control over hedonic behaviors. The rostral shell promotes appetitive behaviors while the caudal shell mediates negative emotional states such as fear and disgust. It is likely that a loss of rostral NAcSh processing accompanied by elevated processing in the caudal NAcSh mediates negative affect. The goal of this proposal is to determine the role of the IL?rostral NAcSh pathway in hedonic processing over CTA learning and extinction. In Aim 1, neural activity (single spikes and local field potential) will be simultaneously recorded in the IL and rostral NAcSh in nave rats, and then over the course of CTA learning and its extinction. It is hypothesized that IL and rostral NAcSh neural activity tracks the rewarding value of sucrose in the nave state (prior to the development of CTA) and during extinction, but fails to exhibit robust activity when sucrose is aversive in CTA. Further, I predict that the strength of connectivity/synchronization (as measured by coherence) between the IL and the caudal NAcSh will be greatest when sucrose is assessed as rewarding (in nave and extinction states), but a loss of synchronization is predicted during CTA. In Aim 2, optogenetics will be utilized to stimulate the IL?rostral NAcSh pathway after CTA learning, to determine if activation of this pathway will functionally suppress conditioned aversion to the sucrose solution. Collectively, these experiments will provide novel insight into ?natural? (nondrug) hedonic processing in the brain and will set the foundation for future experiments that explore the role of the IL?rostral NAc shell circuit in negative affect associated with substance use disorders.